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Biomedical subjects

M Mizuno

Publications and source records attributed to M Mizuno.

At least 559 records · Page 31Linked to original sources

Effectivity of dolichyl phosphates with different chain lengths as acceptors of nucleotide activated sugars.

Chemical synthesis of different S-forms of dolichyl-P was performed in order to investigate the use of these polyprenes in mannosyl, glucosyl and glucosaminyl transferase reactions. Determination of the Vmax values for a series of dolichyl-P demonstrated that the velocities of transferase reactions with all those dolichyl-P derivatives present in animal tissues are largely the same. The apparent Km values for the various dolichyl-P in the transferase system studied differed, but this property does not appear to have physiological importance.

Animals↗

Effects of adenine arabinoside on cellular immune responses in patients with chronic hepatitis B.

The lymphocyte subsets in the peripheral blood and in liver biopsies from 4 patients with chronic hepatitis B obtained about 2-7 weeks before and after treatment with adenine arabinoside (Ara-A) were studied by a peroxidase-labeled antibody method using monoclonal antibodies against Leu-1, Leu-2a, Leu-3a, Leu-7 and Leu-10 antigens. In the peripheral blood, the percentage of Leu-2a+ (cytotoxic/suppressor) cells was significantly reduced and the ratio of Leu-3a+ (helper/inducer) to Leu-2a+ cells was increased after the treatment with Ara-A. In the liver biopsies, the numbers of Leu-1+ (pan T) and Leu-2a+ cells were significantly decreased after the treatment with Ara-A. As a result, the Leu-3a+/Leu-2a+ ratio was significantly elevated in the liver after the therapy. The majority of lymphocytes distributed at sites of hepatocytic necrosis were positive for Leu-2a. The reduced numbers of Leu-1+ and Leu-2a+ cells after the treatment were mainly due to the decrease of these cells infiltrating to the sites of hepatocytic necrosis. The numbers of other subsets (Leu-3a+, Leu-7+ and Leu-10+) changed without any specific tendency both in the peripheral blood and in the liver biopsies after the treatment. With respect to viral replication, most of the patients showed a decrease of serum DNA polymerase activity or demonstrable intrahepatic HBsAg and HBcAg after the treatment. These data suggest that T cell-mediated cytotoxicity against HBV-infected hepatocytes is diminished after treatment with Ara-A.

DNA-Directed DNA Polymerase↗

Development of a monoclonal antibody identifying an antigen which is segregated to the sinusoidal and lateral plasma membranes of rat hepatocytes.

We developed a monoclonal antibody to the plasma membrane of rat hepatocytes. Immunoelectron microscopic characterization of an antigen identified by our antibody revealed that the antigen was present diffusely on the sinusoidal and lateral plasma membranes of hepatocytes but absent from the bile canalicular membrane. Sinusoidal lining cells (Kupffer cells and endothelial cells) were devoid of the antigen. Within hepatocytes, the antigen was present in the Golgi complexes, segments of endoplasmic reticulum and small vesicle-like structures. The development of the monoclonal antibody to the segregated membrane antigen of the hepatocyte in this study provides a reliable marker of specific membrane domains for use of isolation of plasma membrane surfaces and is a useful tool for investigation of the transferring mechanisms of membrane proteins to their destinations.

Animals↗

Metabolism of arachidonic acid and synthesis of prostanoids in human endometrium and decidua.

Arachidonic acid metabolism and prostanoid synthesis were investigated using [14C]-arachidonic acid (AA) in human endometrium obtained at different phases of the ovarian cycle and decidua in early pregnancy. Prostaglandins (PG) identified in endometrium and decidua were PGE2 and PGF2 alpha. The capacity for the production of PGE2 and PGF2 alpha was higher in the secretory phase of endometrium than in the proliferative phase, and the maximum formation of PGE2 and PGF2 alpha was found in the mid secretory phase and in the late secretory phase, respectively. However, the production of PGs was markedly suppressed in decidua. On the other hand, more than 70% of [14C]AA was incorporated into total neutral lipids, whereas less than 22% was incorporated into glycerophospholipids in both endometrium and decidua. Secretory endometrium showed a higher uptake of [14C]AA into glycerophospholipids than did proliferative endometrium, whereas the incorporation into neutral lipids was lower in secretory endometrium than in the proliferative phase. Moreover, decidua showed a similar pattern of incorporation of [14C]AA to the proliferative phase. The changes of arachidonic acid metabolism and PG formation in both endometrium and decidua are discussed in terms of implantation and maintenance of early pregnancy.

Arachidonic Acid↗

Neurotological findings in amyotrophic lateral sclerosis.

Neurotological examinations with special regard to eye movements using electronystagmography (ENG) were performed and analyzed on 22 patients with amyotrophic lateral sclerosis (ALS). Optokinetic nystagmus, pursuit and saccadic eye movements were abnormal in a considerable number of the patients. The incidence of abnormalities correlated to the severity, but not to the duration of illness. The mechanisms of abnormalities of eye movements were considered initially supranuclear, and later both supranuclear and nuclear involvements would play main roles in the appearance of the abnormalities of eye movements.

Adult↗

Characterization of mitomycin C-induced gastrointestinal damage: changes in the gastric absorption of drugs in rats.

The effect of mitomycin C (MMC) pre-administration intravenously on the absorption of drugs from rat stomach has been examined by means of the in-situ loop technique. 48 h after the MMC-treatment, the absorption of salicylic acid, aspirin and sulphanilic acid was not influenced but that of sulphanilamide was significantly increased compared with the control. At 96 h, a differential effect of MMC on the absorption of each drug was seen: the absorption of weakly acidic drugs was significantly decreased while that of bases and strong sulphonic acid increased. The decreased absorption of salicylic acid and aspirin correlated with the reduced gastric mucosal blood flow. At 96 h there were severe haemorrhagic lesions in the gastric mucosae. The increase in absorption of poorly absorbed drugs could be ascribed to the increased permeability of the blood-gastric epithelium barrier as was evidenced by leakage of Evans Blue.

Animals↗

Concentrations and origin of oxytocin in breast milk.

Samples of human milk obtained from lactating women in the early postpartum period were assayed for oxytocin concentrations by specific RIA, following extraction procedures with Florisil. Mean oxytocin concentrations in human milk at postpartum day 1 to 5 were 4.5 +/- 1.1, 4.7 +/- 1.1, 4.0 +/- 1.3, 3.2 +/- 0.4, 3.3 +/- 0.6 microunits/ml (+/- SE), respectively. Oxytocin levels in milk were significantly increased by nursing (3.1 +/- 0.6, 5.3 +/- 1.0 microunits/ml, respectively). 3H-oxytocin in human milk was stable even after incubation at 37 degrees C for 2 hours. The dilution curve for milk was parallel to the curve for the standard oxytocin. The chromatographic fraction of immunoreactive oxytocin was identical to that of 3H-oxytocin. 3H-oxytocin was administered to lactating rats. Radioactivity in the neonatal gastric contents and plasma were 12.8% and 4.4% of the counts in the maternal plasma. It was made clear that oxytocin is stable in milk and that oxytocin in maternal blood can be transferred to mik and then to neonates.

Animals↗

Effect of individual amino acids on plasma cholesterol level in rats fed a high cholesterol diet.

The effect of individual amino acids added to a cholesterol containing casein diet on the plasma cholesterol level of rats was systematically investigated with objective of confirming the possibility that specific amino acids are responsible for the regulation of plasma cholesterol level by dietary proteins. Half the amino acids tested were effective to some degree in influencing the plasma cholesterol level when amino acids were added singly to the diet at a 5% level. However, only sulfur containing amino acids had significant effects when added to the diet at a 1% level; Met enhanced and Cys reduced the plasma cholesterol level. In addition, the results of an experiment with amino acid mixture diets with different Met, Cys, and/or Gly contents indicated the importance of sulfur amino acids and also of Gly in plasma cholesterol regulation. The results obtained here support the notion that the plasma cholesterol level of rats can be influenced by specific amino acids or amino acid compositions of dietary proteins, at least under the experimental conditions used.

Amino Acids↗

[Polycystic ovary--classification and treatment by bromocriptine].

Plasma levels of androstenedione (A) and dehydroepiandrosterone sulfate (DHAS) were measured in 29 women with PCO in an attempt to classify PCO. A and/or DHAS were elevated in all cases. In cases with DHAS levels below 2,000 ng/ml, the A levels were found to be over 1.4 ng/ml. This group was defined as an ovarian type because the major source of A is the ovary. In contrast, women whose DHAS levels were higher than 2,000 ng/ml were classified as an adrenal type. In both groups, the hormonal features were elevated LH levels and exaggerated LH response to LHRH. The mean A levels were 2.43 +/- 0.31 ng/ml in ovarian type and 2.20 +/- 0.42 ng/ml in adrenal type. The mean DHAS levels for the adrenal type were 3,052 +/- 299 ng/ml, or about 3 times as high as normal values. On the other hand, those for the ovarian type were on the upper borderline of the normal range. In both groups, dexamethasone lowered DHAS levels by about 80% with no discernible effect upon A levels. The successful rate for ovulation-induction by clomiphene was 20% in the ovarian and 33% in the adrenal. Bromocriptine induced ovulation in 8 out of 9 cases of the ovarian type. However, only one of 6 responded to bromocriptine in the adrenal type. Bromocriptine-unresponsive cases of the adrenal type ovulated following treatment with combination of clomiphene and prednisolone. In summary, we attempted to classify PCO into ovarian and adrenal types by analyzing the elevated androgen level. This classification seems to be useful in the treatment of PCO and also provides some insight into the pathogenesis of PCO.

Adolescent↗

Partial prevention of compactin (ML-236B) inhibition of in vitro hematopoiesis by dolichol and dolichyl phosphate.

We have reported that the exogenous addition of dolichyl phosphate (Dol-P) enhances the colony-forming capacities of early erythroid progenitors (BFU-E), late erythroid progenitors (CFU-E), and granulocyte-macrophage progenitors (CFU-GM) in adult mouse bone marrow, and that dolichol (Dol) enhances that of only CFU-E (Int. J. Cell Cloning 3:313, 1985). Compactin (2.5-10 microM), a specific inhibitor of mevalonate biosynthesis that causes a decrease of endogenous Dol biosynthesis, inhibited colony formation of CFU-GM. Exogenous addition of Dol-P partially prevented this inhibition, but Dol and the other mevalonate metabolites, such as cholesterol, coenzyme Q10, and isopentenyladenine, could not. In addition, we have found that the colony-forming capacity of CFU-E in fetal mouse liver was not enhanced by exogenous Dol or Dol-P. But the decrease of colony formation or DNA synthesis of fetal CFU-E in the presence of compactin was prevented by the exogenous addition of Dol or Dol-P.

Animals↗

Reaction of optically active S- and R-forms of dolichyl phosphates with activated sugars.

Chemical synthesis was used to produce optically active isomers of dolichol (S- and R-forms) with 18 and 19 isoprene residues. The phosphorylated polyprene was studied in rat liver microsomal GDP-mannosyl and UDP-N-acetylglucosaminyl transferase systems. The two dolichol-P forms in both transferase systems gave Vmax values which for the S-form exceeded 4-6 times what was obtained with the R-form. The Km values were also higher for the S-form. The hepatocyte appears to contain a large excess of dolichyl-P, by 100 times exceeding that of the Km values. For this reason the S-form of dolichyl-P seems to be one of the requirements for the normal establishment of the N-glycosidically linked oligosaccharide chain.

Animals↗